Surgical Biology for the Clinician Biologie chirurgicale pour le …canjsurg.ca/wp-content/uploads/2014/03/41-2-103.pdf · 2014. 3. 13. · Laparoscopy modulates both afferent stimuli

Minimal access surgery hasrevolutionized the treat-ment of many surgical dis-

eases. The rapid acceptance of thistechnique has been fuelled by the im-proved patient morbidity comparedwith that for nonlaparoscopic surgicalprocedures.1–3 Whereas the ability tosuccessfully treat the underlying dis-ease process is equivalent, laparoscopic

treatment of many conditions is asso-ciated with shorter hospital stay and re-duced costs compared with open pro-cedures.2,4 This is due in large part tothe less frequent occurrence of pain,fever and disability.2,5 For example, in arandomized trial comparing laparo-scopic with open cholecystectomy,Barkun and associates5 demonstratedthat the mean duration of postopera-

tive pain and the time to improvementin quality of life were significantlyshorter after laparoscopic surgery. Simi-larly, Goodale and associates6 recentlyshowed that postoperative pain andventilatory capacity were significantlyimproved after laparoscopic cholecys-tectomy. In a trial comparing openversus laparoscopic Nissen fundoplica-tion, Rattner and Brooks7 reported

Surgical Biology for the ClinicianBiologie chirurgicale pour le clinicien

HOST RESPONSE TO LAPAROSCOPIC SURGERY:MECHANISMS AND CLINICAL CORRELATES

David J. Hackam, MD; Ori D. Rotstein, MD

From the Department of Surgery, The Toronto Hospital, and the University of Toronto, Toronto, Ont.

Accepted for publication Nov. 13, 1997

Correspondence to: Dr. Ori D. Rotstein, The Toronto Hospital — General Division, EN 9-232, 200 Elizabeth St., Toronto ON M5G 2C4; tel 416 340-4988; fax 416 595-9486;[email protected]

© 1998 Canadian Medical Association (text and abstract/résumé)

Minimal access surgery has revolutionized the treatment of a variety of surgical diseases, partly because it isassociated with less patient morbidity than nonlaparoscopic surgical procedures. Emerging evidence sug-gests that alteration in the host response after laparoscopic procedures has significantly contributed to theimproved postoperative course. Laparoscopy modulates both afferent stimuli (including tissue trauma, painand wound size) and efferent responses (via neuroendocrine, metabolic, immunologic and cardiorespira-tory systems). These effects lead to a decrease in postoperative pain, fever and disability. Laparoscopy me-diates these effects through reduced wound size, the activities of endotoxin and immunomodulatory ac-tions of the insufflated gas, resulting in impaired macrophage activity. Although clearly beneficial inreducing postoperative morbidity after elective surgery, this immunosuppression could increase the risk ofcomplications during procedures for infection or neoplasia.

La chirurgie avec effraction minimale a révolutionné le traitement de toutes sortes d’affections chirurgi-cales, en partie parce qu’elle cause moins de morbidité chez les patients que les interventions chirurgicalesnon laparascopiques. De plus en plus de données probantes indiquent que l’altération de la réaction del’hôte après les interventions laparoscopiques a beaucoup contribué à améliorer l’évolution postopératoire.La laparoscopie module à la fois les stimuli afférents (y compris les traumatismes tissulaires, la douleur etl’étendue de la plaie), et les réactions efférentes (par les systèmes neuroendocrinien, métabolique, im-munologique et cardiorespiratoire). Ces effets réduisent la douleur, la fièvre et l’incapacité après l’interven-tion. La laparoscopie atténue ces effets en réduisant l’étendue de la plaie, les activités des endotoxines et leseffets immunomodulateurs du gaz insufflé, ce qui inhibe l’activité des macrophages. Même si elle est claire-ment bénéfique en réduisant la morbidité postopératoire après une intervention chirurgicale élective, cetteimmunosuppression pourrait accroître le risque de complications au cours d’interventions pratiquées àcause d’une infection ou d’une néoplasie.

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that postoperative disability, length ofhospital stay and time to return towork were significantly shorter after la-paroscopic surgery. In abdominal la-paroscopic procedures, the dramaticshortening of postoperative convales-cence has been attributed primarily tothe small size of the abdominal wall in-cision with a concomitant reduction inpain. Emerging evidence, however,suggests that alterations in the host im-mune system after laparoscopic proce-dures has also contributed significantlyto the improved postoperative course.This review will highlight the im-munologic responses to abdominal la-paroscopic surgery and attempt to cor-relate these with improved outcomes.

MODULATION OF THE HOSTRESPONSE

After a surgical procedure, the bodymounts a host of targeted responsesthat together serve to maintain home-ostasis and promote healing. The stim-uli that initiate and potentiate these re-sponses have been well characterizedand include the effects of the operativewound, pain, changes in circulatingblood volume and temperature. Thesystemic response to these stimuli oc-curs rapidly and with an intensity ap-propriate to the magnitude of thestimulus. The major changes involveneuroendocrine, metabolic, immuno-logic and cardiorespiratory systems. Tounderstand the mechanisms wherebylaparoscopic surgery modulates thehost response to surgery, a detailed un-derstanding of both the stimuli (i.e.,afferent “triggers”) and systemic re-sponses (i.e., efferent “reflexes”) is crit-ical and is reviewed here (Table I8–45).

Afferent triggers induced byconventional and laparoscopicsurgery

Afferent stimuli induced by surgery

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Table I

Neuroendocrine

Corticotropin-releasinghormone

Increased Increased 19, 23

Modification of Afferent Triggers and Efferent Reflexes by Open and Laparoscopic Surgery

Adrenocorticotropichormone

Unchanged Unchanged 16, 19

Cortisol

Factor

Unchanged Unchanged

Local afferent stimuli

16, 19

Thyroxine

Wound size

Increased Increased

Tissue trauma

17, 18

Growth hormone

Pain

Increased Increased

Distal afferent stimuli

15–17

Metabolic

Gluconeogenesis Increased Increased 15, 24

Insulin resistance Increased Decreased 19, 24, 25

Protein catabolism Increased Decreased 19, 25

Lipid metabolism Increased Decreased 19, 25

Immunologic

Leukocytosis Increased Unchanged 19

Chemotaxis Increased Decreased 23, 26

Superoxide Increased

Increased

Increased

Increased

Open surgery

Decreased 26

Cytokines

Decreased

Increased

Decreased

Laparoscopic surgery

10–14

9

8

Reference nos.

Interleukin-1 Increased Increased/decreased 17, 27, 28

Tumour necrosis factor Increased Increased/decreased 27–32

Interleukin-6 Increased Unchanged 6, 18, 28,33–35

Acute phase proteins Increased Unchanged 34

Cardiorespiratory

Total lung capacity Decreased Decreased 36, 37

Forced vital capacity Decreased Decreased 37–41

Forced expiratoryvolume in 1 s

Decreased

Blood volume

Decreased 37–41

Atelectasis Increased Decreased

Increased Increased 20, 21

Temperature

37–41

Oxygenation Decreased Decreased 37–41

Decreased Decreased 22

Efferent responses

Cardiac output Unchanged Decreased 42–44

Stroke volume Unchanged Decreased 45

Ejection fraction Unchanged Decreased 42–44

may be grouped into those occurringat or adjacent to the operative site(i.e., site-specific stimuli) and thoseoccurring distant from it (i.e., syste -mic stimuli). The predominant site-spe cific stimulus is the wound itself,which activates the host responsethrough the cytokines and other me-diators elaborated by the inflamma-tory cells that migrate to it.8 Bacterialcomponents present in wounds, suchas endotoxins and exotoxins, inducethe release of mediators such as inter-leukin and tumour necrosis factor(TNF) from macrophages and neu-trophils.9 Importantly, these cytokinesmay have immunomodulatory effectson other stimuli, as they have beenshown to alter the pain threshold inrodent models of surgical stress.10 Ofnote is that the size of the stimulus isdirectly related to the size of thewound,8 suggesting that laparoscopicprocedures, which typically utilizesmaller incisions than conventionalprocedures, may be associated withsmaller afferent stimuli.Postoperative pain represents an

additional site-specific trigger, whichacts directly upon the thalamus andhypothalamus through nociceptivefibres11–13 and therefore induces therelease of adrenocorticotropic hor-mone (ACTH), cortisol and endoge-nous opiates. These substances notonly induce the efferent responsesdescribed below but are manifestedas postoperative changes in the pa-tient’s body temperature, appetiteand energy.14 Patients generally re-port less postoperative pain after la-paroscopic surgery than after conven-tional surgery, suggesting that theburden of the circulating levels ofthese hormones may be correspond-ingly decreased.15 Recently, Karayian-nakis and colleagues16 compared theplasma levels of cortisol, adrenalineand noradrenaline after laparoscopiccholecystectomy and conventional

cholecystectomy in a double blindedfashion. Whereas these hormoneswere increased after both procedures,they were significantly higher in theopen cholecystectomy group. Othershave failed to demonstrate significantdifferences in such levels, reflectingperhaps the variable nature of thestress hormone response.17–19

Distant stimuli induced by surgicalprocedures include, predominantly,changes in circulating blood volumeand temperature. Loss of effective cir-culating volume during surgery, asmay occur from bleeding or “thirdspace” fluid shifts, is sensed by pressure-sensitive baroreceptors in theaorta, carotid arteries and renal arter-ies, and by volume-sensitive receptorsin the atria.20 These afferent signals in-duce changes in hormone secretion(ACTH, vasopressin and renin) andsympathetic nervous system activity,6

resulting in the release of cate-cholamines and changes in vasculartone and cardiac output.21 A drop incore temperature is associated withprolonged open abdominal proce-dures. This is sensed in the preopticarea of the hypothalamus and alters thesecretion of hormones, which includeACTH, cortisol, antiviral protein,growth hormone, aldosterone, thyrox-ine and catecholamines. Several au-thors2,22 have reported a high incidenceof hypothermia after laparoscopicsurgery, particularly during the earlyexperience with this technique. Impor-tantly, differences between laparo-scopic and conventional procedureswith respect to the magnitude of fluidshifts and temperature changes havenot been consistently demonstrated.This suggests that although these stim-uli are important triggers for the effer-ent responses described in the nextsection, they cannot readily accountfor the observed differences in postop-erative course between open and la-paroscopic techniques.

Efferent responses to conventionaland laparoscopic surgery

The stimuli we have described in-duce the body to mount a variety ofcellular, biochemical and hormonal re-sponses, the overt manifestations ofwhich are the standard signs of inflam-mation and healing observed in all pa-tients postoperatively. Because theseare reportedly less severe in laparoscop-ically treated patients, it follows that ef-ferent responses may be either attenu-ated or absent in such cases. Therefore,we describe in the following sections,the typical responses occurring in theneuroendocrine, metabolic, immuno-logic and cardiorespiratory systems andthe principal differences between la-paroscopic and conventional surgery.

Neuroendocrine responses

The neuroendocrine responses tosurgical procedures involve the releaseof hormones under hypothalamic, an-terior pituitary and adrenocor -tical control and primarily include corticotropin-releasing hormone(CRH), ACTH and cortisol respec-tively. CRH release in response to thetriggers described above stimulatesACTH release in a process that is po-tentiated by interleukin-1 (IL-1), IL-6 and TNF liberated from inflamma-tory cells.23 Cortisol, the ultimatehormonal product of the neuroen-docrine axis, has pleiotropic effects onthe metabolism of glucose and aminoacids,19 and rises in response to thestress of surgery. The production ofthyroxine from the thyroid gland inresponse to thyroid-stimulating hor-mone augments these effects on cellu-lar metabolism and modulates oxygenconsumption, temperature regulationand activity of the sympathetic ner-vous system. Growth hormone, re-leased by the pituitary in response tohypothalamic growth hormone-

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releasing hormone, is increased aftersurgery and primarily modulates pro-tein synthesis and lipid and carbohy-drate stores to promote healing.Several studies have examined

whether laparoscopy influences theneuroendocrine response by examin-ing serum levels of these hormones.These studies have generated conflict-ing results. Although at least 2 studiescomprising small series with historicalcontrols have identified attenuated re-lease of cortisol and growth hormonesafter laparoscopic procedures,16,19 sev-eral large randomized trials have notsubstantiated these findings.15,17,18 Thevalue of measuring the neuroen-docrine response to laparoscopic andconventional procedures is limited bythe inability to discern whether mea-sured differences are primarily respon-sible for alterations in postoperativeoutcome, or themselves reflect out-comes that are modulated by otherunrelated factors, including those de-scribed below.

Metabolic responses

Surgery induces profound meta-bolic alterations, which are influencedsignificantly by the age and health ofthe patient, the duration of preopera-tive fasting, and the extent and dura-tion of the surgical procedure.24 Al-though a detailed description of theseresponses lies beyond the scope of thisreview, the fundamental changes in-volve an increase in overall energy re-quirements, which are met by in-creased gluconeogenesis, and theutilization of lipid products for primaryenergy sources. This is associated withrelative insulin resistance and an in-crease in protein catabolism.24 Severalauthors have investigated whether la-paroscopic surgery alters the pattern orextent of these metabolic responses.Through a prospective, randomizedtrial, Ortega and colleagues15 com-

pared the metabolic response of pa-tients who underwent elective laparo-scopic cholecystectomy versus thosewho had conventional cholecystec-tomy. They found that circulating glu-cose and insulin levels were signifi-cantly higher after open procedures,suggesting that such procedures exerta greater metabolic load. In support ofthis, studies by Thorell and col-leagues24 demonstrated that relativelyless insulin resistance accompanies la-paroscopic cholecystectomy than opencholecystectomy. Likewise, Glerupand associates19 showed that postoper-ative hepatic nitrogen clearance, ameasure of the catabolic conversion ofamino acids to urea, was significantlyless after laparoscopic surgery than af-ter open cholecystectomy.25 The ma-jority of the evidence therefore sug-gests that laparoscopic surgery isassociated with lower metabolic stressthan open procedures. This findingmay correlate with the clinical obser-vations by Barkun and colleagues5 ofimproved appetite, energy level and re-turn to normal activities after laparo-scopic cholecystectomy However, themechanisms mediating this effectpresently remain unexplored.

Immunologic responses

The immunologic response tosurgery consists of both the cellularand humoral components of the im-mune system. Current dogma sug-gests that inflammatory cells (neu-trophils and macrophages) play acentral role in the local response byvirtue of their ability to coordinate theevents involved in hemostasis, clear-ance of foreign debris and regulationof wound healing. It is therefore plau-sible that laparoscopic surgery mightattenuate the local inflammatory re-sponse to surgery, thereby leading toimprovements in the patient’s postop-erative course. It has been demon-

strated that the numbers of circulat-ing neutrophils and macrophages aresimilar when cholecystectomy is per-formed either laparoscopically or as anopen procedure, suggesting that im-munologic differences lie in the func-tion of these inflammatory cells.19 Insupport of this, the migration of neu-trophils and their secretion of micro-bicidal superoxide anions were de-creased in patients who underwentlaparoscopic cholecyst ectomy com-pared with those who underwentopen cholecystectomy.26 However,elastase release, another measure ofneutrophil function, was similar in pa-tients who underwent laparoscopic oropen hysterectomy,23 revealing thepleiotropic nature of the postoperativeinflammatory response.Cytokines are chemical mediators

that influence a variety of immuno-logic processes and serve as markersof the extent of the inflammatory re-sponse. The effects of laparoscopy onIL-1 have been extensively studied,as this cytokine, which increases T-cell proliferation, induces fever bystimulating prostaglandin release inthe central nervous system and affectsseveral metabolic effects observedpostoperatively. Isolated macro phages exposed to carbon dioxide re-leased lower amounts of IL-1 com-pared with macrophages exposed toother gases, suggesting that this cy-tokine may be attenuated after la-paroscopic surgery.27 However, IL-1release is increased after both openand laparoscopic cholecystectomy,and the pattern of release was similarin both patient groups.17,28 TNF is acytokine that acts alone and synergis-tically with IL-1 to induce hypoten-sion in response to tissue injury.29

TNF levels increase in the postopera-tive period, likely in response tomany of the triggers we have de-scribed.30 In vitro studies have shownthat carbon dioxide exposure de-

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creases TNF production,27,30,31 sug-gesting the possibility that this cy-tokine is decreased after laparoscopicsurgery. Indeed, recent reports haveindicated that TNF levels are lowerafter laparoscopic that after open sur-gical procedures.32 This may not be auniversal phenomenon, as severalstudies have demonstrated that thepattern of postoperative TNF occursindependent of whether laparoscopywas performed.17,46 By contrast, levelsof IL-6, a cytokine that enhances im-mune function and the production ofhepatic acute-phase proteins postop-eratively, have consistently beenshown to be significantly higher afteropen than after laparoscopic chole-cystectomy.6,18,28,33–35 Whereas the clin-ical course suggests that laparoscopicsurgery attenuates the postoperativeimmune profile, current data suggesta lack of consensus with respect tothe majority of the measured parame-ters. It is possible that this variabilityreflects innate differences betweentypes of procedures or patients’ base-line immune status. Alternatively,current measurement techniques maynot adequately assess the dynamicnature of the immune response. Fur-ther studies will be required to re-solve this.

Cardiorespiratory responses

Typical respiratory effects of abdom-inal surgical procedures include reduc-tions in total lung capacity, functionalresidual capacity, forced expiratory vol-ume in 1 second (FEV1), and forced vi-tal capacity (FVC), as well as the radio-logic features of atelectasis. Theseresponses reflect the intraoperative ef-fects of patient positioning and me-chanical ventilation and the postopera-tive effects of incisional pain anddecreased mentation. Laparoscopywould be expected to mitigate such ad-verse respiratory alterations due to the

absence of midline wounds and theconsequent decreased need for postop-erative analgesia. Several reports havecharacterized the respiratory changesoccurring after laparoscopic abdominalprocedures and compared them withconventional operations. Torringtonand colleagues36 showed that atelectasisdevelops in less than one-third of pa-tients who undergo laparoscopic chole-cystectomy, and that decreases in FVCand FEV1 were minor and not associ-ated with clinically important changesin arterial blood gases. Importantly, ina prospective randomized study,Karayiannakis and associates37 deter-mined that laparoscopic cholecystec-tomy was associated with a significantlylower incidence of atelectasis and im-proved pulmonary function test resultsand oxygenation than open cholecys-tectomy (28.6% versus 62.5%), a find-ing that has been confirmed by severalother groups.38–41 Several reports haveidentified that the carbon dioxidepneumoperitoneum causes a respira-tory acidosis, which may pose particu-lar risk for patients with underlying res-piratory disease.47 Interestingly, this riskmay be significantly reduced when he-lium is used as the insufflating agent.47

Changes in hemodynamic functionoccur in association with laparoscopicsurgery in direct response to the in-creased abdominal pressure presentduring insufflation. Routine anestheticmonitoring may not fully reflect thecardiorespiratory effects of laparo-scopic surgery, since determinations ofcardiac output, stroke volume andejection fraction have demonstratedsignificant decreases during abdominalinsufflation.42–44 These effects are com-pounded in elderly patients of higherAmerican Society of Anesthesiologistsclassification and may be worsened byplacing patients in the Trendelenburgposition.44 There is a gradual restora-tion of the cardiac index,45 althoughdecreases in blood pressure remain.

Mechanisms mediating theattenuated immune responseobserved after laparoscopic surgery

Investigative efforts in several cen-tres including our own have begun toshed light on the mechanisms con-tributing to the altered immune state.In general terms, possible mechanismswhereby laparoscopic surgery couldmodulate the immune system includeeither effects of incision size or effectsrelated to the insufflated gas. The ra-tionale for examining the effect of in-cision size on postoperative course isbased on the premise that smaller in-cisions induce less tissue damage thanlarger ones and thus incite a compara-tively less intense local and systemichost response. A recent study compar-ing laparoscopic cholecystectomy to“small incision” open cholecystec-tomy demonstrated an improvedpostoperative course after laparo-scopic surgery despite the fact that thetotal lengths of the incisions werecomparable in the 2 groups.5 Further,laparoscopic appendectomy has beenassociated with shorter hospital stayand recovery time than open proce-dures, although the total incisionlength is similar in the 2 procedures.2

It therefore seems unlikely that inci-sion size alone is responsible for theimproved postoperative outcome andthe attenuated immune response ob-served after laparoscopic surgery.Endotoxin-like contaminants in

circulating air have been proposed toupregulate monocyte and neutrophilactivity, and therefore modulate thepostoperative immune state after opensurgical procedures.48 Accordingly, la-paroscopic procedures that preventexposure to the air would confer aprotective benefit to the patient fromaerosolized factors and thus hypothet-ically account for the improved post-operative outcome.2 However, thelack of an identified aerosolized proin-



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flammatory yet noninfectious agent,as well as the broad disparity withwhich similar quantities of exposed airinduce postoperative inflammatorychanges in open procedures (i.e., bi-lateral mastectomy, aortic aneurysmrepair and liver transplantation) indi-cate that other factors likely are likelymore important.An alternative hypothesis relates to

an immunomodulatory effect of theinsufflated gas itself. It is conceivablethat carbon dioxide insufflated intothe peritoneal cavity could either di-rectly or indirectly attenuate the hostimmune response. Evidence in sup-port of this has been shown byFukushima and associates,49 who com-pared the effects of gas-free laparo-scopic-assisted colectomy (LAS) andopen colectomy on postoperative cy-tokine and stress hormone responses.LAS was performed by a gasless ab-dominal wall-lifting method. Theseauthors determined that there was nodifference in stress responses betweenthe 2 groups,49 in stark contrast to theeffects on these parameters describedabove in association with carbon diox-ide insufflation. Direct evidence thatthis gas directly affects the immune re-sponse of inflammatory cells was re-cently provided by West, Baker andBellingham,27 who showed that iso-lated murine peritoneal macrophagesproduced decreased levels of the cy-tokines TNF and IL-1 when exposedto carbon dioxide compared withother test gases in vitro. Similar find-ings have recently been reported byIwanaka and associates.30 These datastrongly suggest that carbon dioxidemay participate in the attenuated im-mune response observed in patientswhose peritoneal cavities have beenexposed to this gas.Because carbon dioxide is known

to form carbonic acid in vivo, we in-vestigated whether this gas inhibitedthe immune response by acidifying the

immune cells to pH levels belowwhich normal function could oc-cur.50,51 To test this possibility, peri-toneal macrophages from mice wereincubated with carbon dioxide, andthe intracellular pH (pHi) was mea-sured using a pH sensitive fluorescentdye.52 We found that exposure to car-bon dioxide induced a precipitousdrop in pHi to approximately 6.1,53 alevel which completely inhibited cy-tokine production by these cells (Fig.1). To confirm the in vivo significanceof this observation, a rodent model ofcarbon dioxide insufflation was de-signed. Gas insufflation induced anacidification of the peritoneum to ap-proximately 6.0 within 5 minutes ofexposure,53 which was associated witha drop in cytokine production by tis-

sue macrophages. These data supportthe hypothesis that insufflated carbondioxide depresses the local host im-mune system by acidifying the peri-toneal cavity and tissue macrophages,thereby attenuating the postoperativesymptoms of pain, fever and disability.

Clinical implications

The altered immune response ob-served in response to laparoscopicsurgery has obvious benefits from thestandpoint of recovery after an opera-tive procedure. However, importantissues remain regarding the effects oflaparoscopic surgery on other clinicalconditions where the immune systemplays an important role, includingport-site metastases and infectious risk.

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FIG. 1. Cytosolic pH of peritoneal macrophages during insufflation of peritoneal carbon dioxide. Peri-toneal macrophages were adhered to glass coverslips and loaded with the pH sensitive dye 2�,7�-bis(2carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester. Cytosolic pH was determined using fluo-rescent imaging during insufflation of the indicated gases. As can be seen, a rapid and profound cy-tosolic acidification to an intracellular pH of approximately 6.1 occurred during carbon dioxide insuf-flation (squares), yet not during insufflation with air (closed circles) or helium (open circles). Thisrepresentative tracing, which displays the mean cytosolic pH of 12 cells during insufflation, is repro-duced with permission from West MA, Hackam DJ, Baker J, Rodriguez JL, Bellingham J, Rotstein OD.Mechanism of decreased in vitro murine macrophage cytokine release following exposure to carbondioxide: relevance to laparoscopic surgery. Ann Surg 1997;226(2):179-90).

Several reports have documented theincreased spread of abdominal tumoursand localized port-site metastases afterabdominal laparoscopic procedures54,55

Possible mechanisms for this phenome-non include the aerosolization of tu-mour cells during abdominal insuffla-tion, the tracking of tumour along theinstrument to the port sites, and the lo-cal attenuation in immune function andcorrespondingly reduced immunosur-veillance. Data from several studies,however, have largely failed to supportthese possibilities. Whelan and col-leagues56 have utilized in vitro and invivo models to demonstrate that tu-mour cells are not readily aerosolized,even in the high pressure carbon diox-ide environment present during laparo-scopic abdominal surgery.56 Reports ofport-site recurrence after 16 laparo-scopic resections of solid abdominal tu-mours are largely anecdotal and proba-bly such recurrence does not occurmore frequently than local recurrenceat open wound sites.54,55,57–59 Finally, therole of immunomodulation for solid ab-dominal tumours remains largely spec-ulative and should not per se precludelaparoscopic evaluation and treatmentof solid tumours.The identification of a carbon-

dioxide-dependent suppression of thelocal immune response raises the pos-sibility that laparoscopic surgery mightincrease the risk of infectious compli-cations. To address this, Illig and as-sociates60 demonstrated that infectiouscomplications were not increased afterlaparoscopic cholecystectomy, andtherefore alterations in prophylacticantibiotic usage were not justified.These findings have been confirmedby others,61 indicating that the in-creased risk of infection after laparo-scopic surgery is likely to be minimal.

SUMMARY

The wide acceptance of laparo-

scopic surgery is due in part to the im-proved postoperative course observedcompared with open procedures.Emerging evidence has demonstratedthat the reduced duration of pain, dis-ability and earlier return to work ex-perienced by patients is associatedwith an attenuated postoperative im-mune response. Studies from severalinstitutions indicate that this may be adirect result of the effects of the insuf-flated gas, which may directly inhibitinflammatory cell activity. It thereforefollows that the role of laparoscopicsurgery in immunosuppressed pa-tients, including those with malignantdisease requires careful analysis andfurther study.

Supported by grants from the Medical Re-search Council of Canada. D.J.H. is the recip-ient of a postdoctoral fellowship from theMedical Research Council of Canada, and anEthicon-Society of University Surgeons re-search award.

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SESAP Critique / Critique SESAPITEMS 531 AND 532

This elderly patient with acute lower extremity ischemia is at risk for significant operative mortality or limb loss with im-mediate operative intervention consisting of Fogarty catheter thrombectomy or arterial revascularization. Operativemortality in the range of 15% to 25% and amputation rates of 25% to 35% have been reported for similar groups of pa-tients. Systemic thrombolytic therapy has been attempted in such patients to reduce the need for immediate operation;however, the bleeding complications of such approaches have been formidable. Selective thrombolytic therapy adminis-tered by intra-arterial catheter at the site of arteriographically demonstrated occlusion is effective in patients with limb-threatening acute lower extremity ischemia, and the total systemic dosage of thrombolytic agent can be reduced to min-imize the bleeding complications. Urokinase, streptokinase, or tissue plasminogen activator can be used for this purpose.The success of such therapy is enhanced in the presence of adequate collateral around the acute occlusion and a singlesegmental occlusion below the femoral artery, both of which are present in this patient. Failure of thrombolytic therapyis more common with aortic or iliac occlusions or when thrombosis occurs in a prosthetic arterial graft.The second arteriogram demonstrates a short segment stenosis of the superficial femoral artery that is unlikely to

improve with additional thromobolytic therapy. This stenosis is the likely cause of the proximal arterial thrombosis thatwas dissolved with the intra-arterial thrombolytic therapy used. Percutaneous transluminal angioplasty is advisable to avoid future recurrent thrombosis and to avoid the operative mortality of vascular reconstruction. Intra- arterial thrombolytic therapy and subsequent percutaneous transluminal angioplasty can reduce the mortality of acutelower limb ischemia to less than 2% and the amputation rate to less than 10%.

531 D 532 B References531–532/1. McNamara TO, Bomberger RA, Merchant RF: Intra-arterial urokinase as the initial therapy for acutely ischemic lower limbs. Circulation 83:106–119, 1991531–532/2. Sicard GA, Schier JJ, Trotty WG, et al: Thrombolytic therapy for acute arterial occlusion. J Vasc Surg2:65–78, 1985

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